In recent years, significant progress has been made towards the chemotherapy (and prophylaxis) of HIV infections. This progress is situated at three different levels. (i) New anti-HIV drugs have been approved for clinical use and have entered the market: the virus entry inhibitor enfuvirtide (Fuzeon), the nucleoside reverse transcriptase inhibitor (NRTI) emtricitabine (Emtriva), the nucleotide reverse transcriptase inhibitor (NtRTI) tenofovir disoproxil fumarate (Viread trade mark ) and the HIV protease inhibitor (PI) atazanavir (Reyataz trade mark ). (ii) Other compounds have proceeded through preclinical and/or clinical development: CXCR4 antagonists (i.e. AMD070), CCR5 antagonists (i.e. SCH-C), NRTIs (such as amdoxovir), NNRTIs (such as etravirine), integrase inhibitors (such as S-1360) and PIs (such as tipranavir). (iii) Yet other compounds, acting by novel mechanisms, have recently been identified as anti-HIV agents that seem worthy of further (pre)clinical development: cell receptor CD4 down-modulators (i.e. cyclotriazadisulfonamides), viral envelope gp120-binding agents such as plant lectins and glycopeptide antibiotics, HIV integrase inhibitors such as the pyranodipyrimidine V-165, and two new classes of compounds (i.e. N-aminoimidazoles and pyridine oxide derivatives) which seem to interfere with a post-integration, transcription transactivation event. Taken together, it is obvious that the approaches for the treatment of HIV infections in recent years have become both more diverse and more efficient.